Temperature 7 Acid Cooling

In a 1 or 1-5 htre round-bottomed flask prepare a solution of 53-5 g. of o-toluidine in 170 ml. of 48 per cent, hydrobromic acid, cool to 5° by immersion in a bath of ice and salt. Diazotise by the gradual addition of a solution of 36 -5 g. of sodium nitrite in 50 ml. of water stopper the flask after each addition and shake until all red fumes are absorbed. Keep the temperature between 5° and 10°. When the diazotisation is complete, add 2 g. of copper powder or copper bronze, attach a reflux condenser to the flask, and heat very cautiously on a water bath. Immediately evolution of gas occurs, cool the flask in crushed ice unless the... 

Cautiously add 250 g. (136 ml.) of concentrated sulphuric acid in a thin stream and with stirring to 400 ml. of water contained in a 1 litre bolt-head or three-necked flask, and then dissolve 150 g. of sodium nitrate in the diluted acid. Cool in a bath of ice or iced water. Melt 94 g. of phenol with 20 ml. of water, and add this from a separatory funnel to the stirred mixture in the flask at such a rate that the temperature does not rise above 20°. Continue the stirring for a further 2 hours after all the phenol has been added. Pour oflF the mother liquid from the resinous mixture of nitro compounds. Melt the residue with 500 ml. of water, shake and allow the contents of the flask to settle. Pour oflF the wash liquor and repeat the washing at least two or three times to ensure the complete removal of any residual acid. Steam distil the mixture (Fig. II, 40, 1 or Fig. II, 41, 1) until no more o-nitrophenol passes over if the latter tends to solidify in the condenser, turn oflF the cooling water temporarily. Collect the distillate in cold water, filter at the pump, and drain thoroughly. Dry upon filter paper in the air. The yield of o-nitrophenol, m.p. 46° (1), is 50 g. 

To prepare pure anhydrous o-benzoylbenzoic acid, dissolve the air-dried (or the moist) product in about 175 ml. of benzene contained in a 500 ml. round-bottomed flask fitted with a reflux condenser and heat on a water bath. Transfer the benzene solution to a separatory funnel, run oflF any water present, and dry with anhydrous magnesium sulphate. Concentrate the benzene solution to about 75 ml. and add light petroleum, (b.p. 60-80°) to the hot solution until a slight turbidity is produced. Allow to cool spontaneously to room temperature, then cool in ice to about 5°, collect the crystals and dry. The yield of pure, anhydrous o-benzoylbenzoic acid, m.p. 128°, is 32 g. 

Evidence from the viscosities, densities, refractive indices and measurements of the vapour pressure of these mixtures also supports the above conclusions. Acetyl nitrate has been prepared from a mixture of acetic anhydride and dinitrogen pentoxide, and characterised, showing that the equilibria discussed do lead to the formation of that compound. The initial reaction between nitric acid and acetic anhydride is rapid at room temperature nitric acid (0-05 mol 1 ) is reported to be converted into acetyl nitrate with a half-life of about i minute. This observation is consistent with the results of some preparative experiments, in which it was found that nitric acid could be precipitated quantitatively with urea from solutions of it in acetic anhydride at —10 °C, whereas similar solutions prepared at room temperature and cooled rapidly to — 10 °C yielded only a part of their nitric acid ( 5.3.2). The following equilibrium has been investigated in detail ... 

For the HCI salt Do exactly as above except use 6N Hydrochloric Acid. 6N HCI may be produced by diluting 60.4mL of "Muriatic Acid" to lOOmL with distilled water. Evaporate the bubbler solution to dryness then add 15ml of water, lOmL 10% NaOH soln. and heat gently to a boil with constant motion until dense white fumes appear. This will remove the Ammonium Chloride. Remove from heat while stirring as it cools down. Pulverize the dry residue, then reflux with absolute Ethanol for several minutes. Filter the refluxed soln. on a heated Buchner or Hirsch funnel, then distill the alcohol off the filtrate until crystals just begin to form. Allow the soln. to cool naturally to room temperature, then cool further in an ice bath. Filter the solution on a chilled Buchner funnel with suction. The yield of Meth iamine Hydrochloride should be around 55% of the theoretical. 

To a solution of 112 (2.0 g, 43.0 mmol) in 50 mL of dry THF at -65°C was added a solution of 111 (4.45 g, 34.0 mmol) in 100 mL of absolute ethanol containing 5 mL of acetic acid cooled to - 65°C in one portion. After stirring for 15 min., dry triethylamine (4.8 g, 510 mmol) was added. The reaction continued for 24 h with slow warming to room temperature before reducing the volume to 10 mL. The crude 113 was brought to pH 10 with potassium carbonate. The aqueous solution was continuously extracted with chloroform, dried (K2CO3), evaporated onto neutral alumina, placed on a column of neutral alumina (50 g) and eluted with chloroform. The solvent was evaporated and the residue crystallized from ethanol to yield 113 (2.86 g 55%). The yellow solid had a mp = 72.5-73.8°C. 

Procedure The crude product from (A) is suspended in the hydrochloric acid, cooled in an ice-salt mixture, and chlorine is passed Into the mixture with stirring for A to 1 hour. Transient blue and green colors may be noticed in the mixture during this time. The temperature will probably rise to 3° to S C. The solid is collected by suction filtration and dried for an hour or so on the filter before use in (C). If at all possible, it should be used on the day of preparation. Yield is 71 grams (after Vh hours on the filter). 

To cold diionyl chloride (1.31 g, 11 mmol) in an ice-water bath, pyridine (10 mL) is added slowly for 10 min to keep the reaction temperature low. The reaction medium is stirred for 30 min. Then, a mixture of isophdialic acid (0.41 g, 2.5 mmol) and terephdialic acid (0.41 g, 2.5 mmol) in pyridine (10 mL) is added slowly for 10-20 min to control the reaction temperature. The cooling badi is then removed and the reaction mixture is stirred at room temperature for 20 min. 2,2-Bis(4-hydroxyphenyl)propane (bisphenol-A, 1.14 g, 5 mmol) in pyridine (10 mL) is added all at once to the mixture, and the whole solution is heated to 80°C (bath temperature) for 4 h. The resulting viscous solution is diluted with pyridine and poured into methanol to precipitate the polymer, which is washed in boiling methanol and dried. The inherent viscosity of polymer is 2.2 dL/g (determined in 60/40 phenol-1.1.2.2-tetrachloroethane at 30°C)... 

A microreactor was also applied to this reaction. The slit interdigital micromixer was purchased from IMM (Mainz, Germany). The width of the interdigital channels is 25 pm. HPLC pumps were used to feed the two reaction solutions. One is a mixture of Boc-AMP and 1.2 molar equivalents of r-BocaO. The other is a 50% aqueous KOH solution. The microreactor was immersed in a temperature controlled cooling bath at 15 °C. The product was quenched with an acid, and samples were taken for HPLC analysis. 

The platinum asbestos is removed by filtration and the product which has deposited on this catalyst is dissolved in water. Alcohol is added to the combined filtered solution and washings, and the mixture is cooled with ice to precipitate the product. A second crop of crystals may be obtained by concentrating the solution under vacuum at room temperature, then cooling and adding hydrochloric acid until the pH is below 1. The crystals are thoroughly washed with ethanol. 

The crude product may be recrystallized by dissolving it in a minimum amount of 1 N hydrochloric acid at room temperature and cooling in an ice bath to 0°. Concentrated hydrochloric acid is added slowly, 0.5 ml. at a time, until the initial volume is approximately doubled. Crystals are removed by filtration and washed with ethanol and diethyl ether. In a typical run the crude yield is 10.3 g. or 70%, and the recrystallized yield is 7.7 g. or about 53%. 

Cyclobutylcyclopropanol [133] To a well-stirred solution of ethyl cyclobutanecarboxylate [134] (56.47 g, 0.441 mol) and titanium tetraisopropoxide (26.3 mL, 88.2 mmol, 20 mol%) in anhydrous diethyl ether (200 mL), ethylmagnesium bromide (0.980 mol, 276 mL of a 3.55 m solution in Et20) was added over a period of 3 h. The temperature was maintained at between 20 and 25 °C with a water bath. After the addition was complete, the mixture was stirred for an additional 0.5 h at the same temperature, then cooled to —5 °C, whereupon the reaction was quenched by the careful addition of ice-cold 10 % aqueous sulfuric acid (500 mL) while the temperature was maintained between —5 and 0°C with an acetone/dry ice bath. The mixture was stirred at 0°C for an additional 1 h and then the aqueous phase was extracted with Et20 (100 mL). The combined ethereal phases were washed with saturated aq. NaHC03 solution (2 X 200 mL) and brine (200 mL), dried, and concentrated at water-pump pressure at 20 °C to give 48.92 g (99%) of 1-cyclo-butylcyclopropanol. The spectroscopic data of the product were identical to those reported in the literature [135]. 

Dissolve 35 g 5-methoxy-DMT (or analog) in 100 ml glacial acetic acid, cool to 10°, stir and add dropwise a solution of 30 ml concentrated HN03 in 50 ml glacial acetic acid over one-half hour. Let warm to room temperature, stir eight hours and dilute with 1 L ice-water. Filter, wash precipitate with water and dry to get 4.5 g 5-methoxy-4-N 02-DMT (recrystallize-methanol). 

Prepare 6-methoxy-l-indanone (I) (JCS 1986(1962)) using polyphosphoric acid made by diluting 500 g of the commercial acid with 120 g 85% phosphoric acid. 2.5 g (I) in 176 ml ether and reflux one hour with 0.27 g lithium aluminum hydride. Cool and carefully add water and filter when bubbling stops (can use Celite filter aid). Dry and evaporate in vacuum and store twelve hours at -15° (under N2 if possible) to precipitate the white 6-methoxy-l-indanol (II) (recrystallize-n-hexane). 2.5 g (II) in 73 ml benzene and reflux one-half hour with 0.2 g p-toluenesulfonic acid. Cool, add water and separate the phases. Extract the aqueous phase with ether and combine with benzene phase and dry, evaporate in vacuum to get 5-methoxy-indene (III) (can distill 110-45/10). 1.53 g (III) and 1.39 g N.N-diethyl-aminoethyl-Cl.HCI in benzene (prepare the free base in benzene as described previously). Reflux four hours with 0.42 g sodamide, cool, wash with water and dry, evaporate in vacuum to get the indene analog of 6-methoxy DET as a dark liquid (can crystallize as oxalate). Alternatively, dissolve 2.51 g (III) in ether and treat (under N if possible) with 12 ml 1.6M buty-Li in hexane at 0-10°. After two hours cool to -30° and add 12 ml more of butyl-Li. Add ether suspension of 2.5 g N,N-diethylaminoethyl-CI. HCI over one-half hour and warm to room temperature. Filter, evaporate in vacuum to get the 6-methoxy-DET analog. 

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